HSV-1 and HSV-2 are related viruses which have similar genomic organization, biological properties and clinical patterns, however, they have undergone sufficient genetic divergence to be recognized as two distinct viruses. It is the goal of these studies to understand the basis of that divergence by focusing on four proteins encoded by HSV-2 and their HSV-1 homologues. The proteins chosen represent the full spectrum ranging from a protein that is extremely type-specific, has been implicated in morphological transformation, and has a molecular weight of 38,000 daltons, to the major DNA binding protein which is highly conserved among the herpesviruses. Also to be studied are two proteins intermediate in their antigenic relatedness, glycoprotein C and thymidine kinase. To achieve this goal we will determine the entire nucleotide sequence of these four genes and their adjacent regulatory sequences in both HSV-1 and HSV-2. This data will be used to predict the amino acid sequence of the proteins and to determine the extent of nucleic acid divergence. To measure intratypic variation small stretches of DNA sequence will be determined from clinical isolates of HSV-1 and HSV-2. Using monoclonal antibodies we will measure the humoral antibody response to these proteins in patients at all stages of herpetic disease. The information obtained will allow us to generate fragments of DNA, polypeptides, and antibodies that are type-specific and will be useful tools in assaying clinical samples.